 2013 Genentech USA, Inc. All rights reserved. Disclosure/Disclaimer The Molecular Biomarkers in Cancer (MBiC) slide presentation is not an independent educational program, and no CME credits will be provided. This program is not intended to promote any cancer agent or class approved by the FDA/EMA or currently under clinical development. The contents of this slide presentation are owned solely by Genentech; any unauthorized uses are prohibited. This program is presented on behalf of Genentech and the information presented is consistent with FDA guidelines. The following slides are selected samples from a complete presentation. They are for educational purposes only. BIO

© 2013 Genentech USA, Inc. MBiC Program 2 Types of cancer biomarkers and their utility Ludwig JA, Weinstein JN. Nat Rev Cancer. 2005;5: Vogelstein B, et al. Nat Med. 2004;10: Initiating events Earliest molecular detection Earliest clinical detection Typical intervention Disease burden Cost / irreversibility Screening Screening diagnostic Prognostic Monitor progression Predictive Resistance Second-line treatment Biomarkers can play a significant role during the clinical management of cancer. Reference: Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5: Notes

© 2013 Genentech USA, Inc. MBiC Program 3 Methods of biomarker detection Cancer cellsNormal cells Isolate mRNAs Make red and green fluorescent cDNAs Analyze data Tumor gene expression Hybridization Microarrays Yang YH, Speed T. Nat Rev Genet. 2002;3: cDNA microarrays provide a powerful tool for studying differential changes in gene expression patterns across a variety of tumor samples. Reference: Yang YH, Speed T. Design issues for cDNA microarray experiments. Nat Rev Genet. 2002;3: Notes

© 2013 Genentech USA, Inc. MBiC Program 4 Measuring the risk of metastatic potential A simultaneous measurement of 70 cancer-related genes in tumor specimens by microarray technology –Evaluates genes involved in cell-cycle regulation, angiogenesis, invasion, signal transduction, and migration Test measures the 10-year risk of metastasis for women with lymph- node–negative, ER–positive, or ER–negative disease Potential markers for metastasis Low risk No metastatic potential; conservative therapy possible High risk Metastatic potential; aggressive therapy needed Cancer biopsy ER=estrogen receptor. van't Veer LJ, Bernards R. Nature. 2008;452: Ma L, Weinberg RA. Trends Genet. 2008;24: Adapted from Weinberg. Sci Am. 1996;275: Cancer Patient A Cancer Patient B Cancer biopsy An expression signature determined through the 70-gene microarray test can be used to stratify patients into high- and low-risk groups. Reference: Ma L, Weinberg RA. Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet. 2008;24: Notes